Cilostazol improves outcome after subarachnoid hemorrhage: a preliminary report

Background: Cerebral vasospasm (VS) is the most common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Reversal of VS by intra-arterial infusion of cyclic adenosine monophosphate (cAMP)-elevating agents has been reported; however, the preventive role in the development of VS is not fully understood. This study is designed to evaluate the possible efficacy of using cilostazol, a selective inhibitor of phosphodiesterase type 3 and a cAMP-elevating agent, in patients with SAH.

Methods: In this prospective randomized study, we enrolled 100 SAH patients who met the following criteria: neck clipping within 72 h after onset, Hunt and Hess (HH) score ≤4, modified Rankin scale (mRS) score ≤2 prior to ictus, and no serious cardiovascular complications. Patients were divided into control and cilostazol groups; we focused on the effects of cilostazol on the decrease in the incidence of symptomatic VS, cerebral infarction, and the mRS score at discharge.

Result: Patients' age, male/female ratio, mRS score prior to ictus, HH grade, Fisher group, site of the aneurysm, drugs prescribed during the observation period, and length of hospital stay were not different between the groups. Cilostazol did not significantly decrease the incidence of symptomatic VS (37.3% in the control vs. 22.4% in the cilostazol group, p = 0.183) and cerebral infarction (27.5% in control vs. 10.2% in the cilostazol, p = 0.091). However, mRS score was significantly improved at discharge (2.6 in controls vs. 1.5 in the cilostazol group, p = 0.041). Patients' age being ≤65 years (OR = 8.47, 95% CI = 2.45-29.32, p = 0.0007), Fisher group ≤3 (OR = 4.64, 95% CI = 1.00-21.45, p = 0.049), HH grade ≤2 (OR = 4.31, 95% CI = 1.27-14.59, p = 0.019), no hydrocephalus (OR = 8.55, 95% CI = 1.72-19.23, p = 0.0046), and cilostazol use (OR = 5.52, 95% CI = 1.61-18.90, p = 0.0065) were independent predictors of good outcomes (mRS score ≤2).

Conclusion: Cilostazol may improve outcomes after SAH, but further double-blind, placebo-controlled studies are required for a definitive conclusion.